Drug development to overcome resistance to EGFR inhibitors in lung and colorectal cancer

► KRAS and secondary EGFR mutations confer resistance to EGFR inhibitors. ► Upregulation of parallel signaling pathways is a frequent adoptive response. ► Irreversible EGFR TKIs may overtake resistance in lung cancer. ► More efficient anti-EGFR mAbs are promising agents in colorectal cancer. ► Combination of targeted agents is a straightforward approach under investigation.